rs17673165

Variant names:

• chr2-9295012-A-G
• rs17673165
• NM_003887.3:c.200-2288A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003887.3(ASAP2):​c.200-2288A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,136 control chromosomes in the GnomAD database, including 3,614 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3614 hom., cov: 33)
• Consequence: ASAP2 NM_003887.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 2 publications found

Genes affected

ASAP2 (HGNC:2721): (ArfGAP with SH3 domain, ankyrin repeat and PH domain 2) This gene encodes a multidomain protein containing an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology (PH) domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal Src homology 3 (SH3) domain. The protein localizes in the Golgi apparatus and at the plasma membrane, where it colocalizes with protein tyrosine kinase 2-beta (PYK2). The encoded protein forms a stable complex with PYK2 in vivo. This interaction appears to be mediated by binding of its SH3 domain to the C-terminal proline-rich domain of PYK2. The encoded protein is tyrosine phosphorylated by activated PYK2. It has catalytic activity for class I and II ArfGAPs in vitro, and can bind the class III Arf ARF6 without immediate GAP activity. The encoded protein is believed to function as an ARF GAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. In addition, it functions as a substrate and downstream target for PYK2 and SRC, a pathway that may be involved in the regulation of vesicular transport. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003887.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASAP2	NM_003887.3	MANE Select	c.200-2288A>G		intron	N/A	NP_003878.1	O43150-1
	ASAP2	NM_001135191.2		c.200-2288A>G		intron	N/A	NP_001128663.1	O43150-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASAP2	ENST00000281419.8	TSL:1 MANE Select	c.200-2288A>G		intron	N/A	ENSP00000281419.3	O43150-1
	ASAP2	ENST00000315273.4	TSL:1	c.200-2288A>G		intron	N/A	ENSP00000316404.4	O43150-2
	ASAP2	ENST00000865541.1		c.233-2288A>G		intron	N/A	ENSP00000535600.1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31712 AN: 152018 Hom.: 3614 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.0306

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.198

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.208 AC: 31716 AN: 152136 Hom.: 3614 Cov.: 33 AF XY: 0.204 AC XY: 15166 AN XY: 74378

African (AFR) AF: 0.143 AC: 5947 AN: 41504

American (AMR) AF: 0.165 AC: 2519 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 631 AN: 3468

East Asian (EAS) AF: 0.0307 AC: 159 AN: 5184

South Asian (SAS) AF: 0.123 AC: 594 AN: 4824

European-Finnish (FIN) AF: 0.263 AC: 2780 AN: 10568

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18326 AN: 67974

Other (OTH) AF: 0.196 AC: 414 AN: 2110

Alfa AF: 0.216 Hom.: 1406

Bravo AF: 0.198

Asia WGS AF: 0.0910 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
DANN	Benign	0.68
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17673165; hg19: chr2-9435141;